A Phase III Parallel Group Study, Comparing the Efficacy, Safety and Tolerability of the Fixed Dose Combination (FDC) of Fluticasone Furoate+Umeclidinium Bromide+Vilanterol (FF/UMEC/VI) With the FDC of FF/VI in Subjects With Inadequately Controlled Asthma

Asthma Clinical Trial

Official title:

A Phase III, Randomized, Double-blind, Active Controlled, Parallel Group Study, Comparing the Efficacy, Safety and Tolerability of the Fixed Dose Combination FF/UMEC/VI With the Fixed Dose Dual Combination of FF/VI, Administered Once-daily Via a Dry Powder Inhaler in Subjects With Inadequately Controlled Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02924688
• Other study ID #: 205715
• Secondary ID: 2016-001304-37
• Status: Completed
• Phase: Phase 3
• Start date: October 13, 2016
• Est. completion date: February 22, 2019

Study information

• Verified date: February 2021
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A once-daily 'closed' triple FDC therapy of FF/UMEC/VI via a single ELLIPTA® dry powder inhaler (DPI) is being developed by GlaxoSmithKline (GSK) with the aim of providing a new treatment option for the management of asthma by improving lung function, health-related quality of life (HRQoL) and symptom control over established combination therapies. This is a phase III, multi-center, active-controlled, double-blind, parallel-group study to compare the efficacy, safety and tolerability of the FDC of FF/UMEC/VI with the FDC of FF/VI. This study has 5 phases: Pre-Screening (Visit 0), Screening/Run-in, Enrolment/Stabilization, Randomization/Treatment, and Follow up. At Visit 1 (Screening), subjects meeting all protocol defined inclusion/exclusion criteria will enter a 3-week run-in period and will receive fixed dose inhaled corticosteroid/long-acting beta agonist (ICS/LABA) (fluticasone/salmeterol, 250/50 micrograms (mcg), via the DISKUS® DPI) one inhalation twice a day. At Visit 2 (Enrolment), eligible subjects will be enrolled into the 2-week stabilization period to receive FF/VI (100/25 mcg via the ELLIPTA DPI once a day, in the morning). At the conclusion of the stabilization period (Visit 3), all subjects who meet the pre-defined randomization criteria will be randomized 1:1:1:1:1:1 during the treatment period to receive either FF/UMEC/VI (100/62.5/25 mcg; 200/62.5/25 mcg; 100/31.25/25 mcg; 200/31.25/25 mcg) or FF/VI (100/25 mcg; 200/25 mcg) via the ELLIPTA DPI once daily in the morning. The duration of the treatment period is variable but will be a minimum of 24 weeks and a maximum of 52 weeks. Subjects will have up to 6 on-treatment clinic visits scheduled at Visits 3, 4, 5, 6, 7 and 8/End of Study (EOS) (Weeks 0, 4, 12, 24, 36 and 52, respectively). A follow-up visit will be conducted approximately 7 days after the end of treatment period or, if applicable, after the early withdrawal visit. Subjects will be provided with short acting albuterol/salbutamol to be used on an as-needed basis (rescue medication) throughout the study. Approximately 2250 subjects will be randomized, with approximately 375 subjects randomized to each of the 6 double-blind treatment arms to ensure approximately 337 evaluable subjects per treatment arm. DISKUS and ELLIPTA are registered trademarks of GSK groups of companies.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2436
• Est. completion date: February 22, 2019
• Est. primary completion date: February 22, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria for Screening

• Age: 18 years of age or older at the time of signing the informed consent.
• Diagnosis: Subjects with a diagnosis of asthma as defined by the National Institutes of Health at least one year prior to Visit 0.
• Symptomatic: Subjects with inadequately controlled asthma (ACQ-6 score >=1.5) despite ICS/LABA maintenance therapy at Visit 1.
• Asthma Control: In the 1 year prior to Visit 1
• A documented healthcare contact for acute asthma symptoms or
• A documented temporary change in asthma therapy for acute asthma symptoms, according to a pre-specified asthma action plan (or equivalent)
• Current Asthma Maintenance Therapy: Subjects are eligible if they have required daily ICS/LABA for at least 12 weeks prior to Visit 0 with no changes to maintenance asthma medications during the 6 weeks immediately prior to Visit 0 (including no changes to a stable total dose of ICS of >250 mcg/day fluticasone proprionate [FP, or equivalent]).
• Spirometry: A best pre-bronchodilator morning (ante meridian [AM]) FEV1 >=30% and <85% of the predicted normal value at Visit 1. Predicted values will be based upon the European Respiratory Society (ERS) Global Lung Function Initiative.
• Reversibility of Disease: airway reversibility defined as >=12% and >=200 milliliter (mL) increase in FEV1 between 20 and 60 minutes following 4 inhalations of albuterol/salbutamol aerosol at Visit 1.
• If the subject does not meet the above reversibility criteria at Visit 1 then the reversibility assessment may be repeated once within 7 days of Visit 1 if either criteria a) or b) are met: a) >=9% increase in FEV1 between 20 and 60 minutes following 4 inhalations of albuterol/salbutamol aerosol at Visit 1. b) Documented evidence of a reversibility assessment within 1 year prior to Visit 1 which demonstrated a post-bronchodilator increase in FEV1 of >=12% and >=200 mL. Should the subject successfully demonstrate airway reversibility (defined as >=12% and >=200 mL increase in FEV1 between 20 and 60 minutes following 4 inhalations of albuterol/salbutamol aerosol) at the second attempt then, provided that all other eligibility criteria assessed at Visit 1 are met, the subject may enter the 3-week run-in period.
• Short-Acting beta2 Agonists (SABAs): All subjects must be able to replace their current SABA inhaler with albuterol/salbutamol aerosol inhaler at Visit 1 as needed for the duration of the study. Subjects must be judged capable of withholding albuterol/salbutamol for at least 6 hours prior to study visits.
• Male or eligible Female, defined as having documentation of non-reproductive potential or reproductive potential as follows: A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin (hCG) test), not lactating, is not planning on becoming pregnant during the study and at least one of the following conditions applies: Non-reproductive potential defined as pre-menopausal females with documented tubal ligation or documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion or hysterectomy or documented bilateral oophorectomy; Postmenopausal defined as 12 months of spontaneous amenorrhea with an appropriate clinical profile (e.g., age appropriate, >45 years, in the absence of hormone replacement therapy). In questionable cases for women <60 years of age, a blood sample with simultaneous follicle stimulating hormone and estradiol falling into the central laboratory's postmenopausal reference range is confirmatory. Females under 60 years of age, who are on hormone replacement therapy (HRT) and whose menopausal status is in doubt, are required to use a highly effective method to avoid pregnancy if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. For most forms of HRT, at least 2 to 4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, subjects can resume use of HRT during the study without use of a highly effective method to avoid pregnancy; Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from the screening visit until after the last dose of study medication and completion of the follow-up visit. The Investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
• Informed Consent: Able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form and in this protocol. Subjects must be able to read, comprehend, and write at a level sufficient to complete study related materials. Exclusion Criteria for Screening
• Pneumonia: Chest X-ray documented pneumonia in the 6 weeks prior to Visit 1.
• Asthma Exacerbation: Any asthma exacerbation requiring a change in maintenance asthma therapy in the 6 weeks prior to Visit 1. Note: Subjects requiring a temporary change in asthma therapy (e.g., oral corticosteroids or increased dose of ICS) to treat an exacerbation in the 6 weeks prior to Visit 1 are not explicitly excluded at Visit 1 provided that, at the Investigator's discretion, the subject's condition is stable after they have resumed their pre-exacerbation maintenance asthma therapy (without modification) and they are considered appropriate for enrolment into this study of up to 12 month's duration.
• Chronic Obstructive Pulmonary Disease: Subjects with the diagnosis of chronic obstructive pulmonary disease, as per Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, including history of exposure to risk factors (i.e., especially tobacco smoke, occupational dusts and chemicals, smoke from home cooking and heating fuels) and a post-albuterol/salbutamol FEV1/Forced Vital Capacity (FVC) ratio of <0.70 and a post-albuterol/salbutamol FEV1 of =<70% of predicted normal values and onset of disease >=40 years of age.
• Concurrent respiratory disorders: Subjects with current evidence of pneumonia, active tuberculosis, lung cancer, significant bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases or abnormalities other than asthma.
• Risk Factors for Pneumonia: Immune suppression (e.g., human immunodeficiency virus, Lupus) or other risk factors for pneumonia (e.g., neurological disorders affecting control of the upper airway, such as Parkinson's Disease, Myasthenia Gravis).
• Patients at potentially high risk (e.g., very low body mass index (BMI), severely malnourished, or very low FEV1) will only be included at the discretion of the Investigator.
• Other diseases/abnormalities: Subjects with historical or current evidence of clinically significant cardiovascular, neurological, psychiatric, renal, hepatic, immunological, gastrointestinal, urogenital, nervous system, musculoskeletal, skin, sensory, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled. Significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study.
• Unstable liver disease as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices or persistent jaundice, cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). Note: Chronic stable hepatitis B and C are acceptable if the subject otherwise meets entry criteria.
• Clinically significant Electrocardiogram abnormality: Evidence of a clinically significant abnormality in the 12-lead ECG performed during screening. The Investigator will determine the clinical significance of each abnormal ECG finding in relation to the subject's medical history and exclude subjects who would be at undue risk by participating in the trial. An abnormal and clinically significant finding is defined as a 12-lead tracing that is interpreted as, but not limited to, any of the following: Atrial fibrillation (AF) with rapid ventricular rate >120 Beats Per Minute (BPM); sustained or non-sustained ventricular tachycardia (VT); Second degree heart block Mobitz type II and third degree heart block (unless pacemaker or defibrillator had been inserted); QT interval corrected for heart rate by Fridericia's formula (QTcF) >=500 milliseconds (msec) in subjects with QRS <120 msec and QTcF >=530 msec in subjects with QRS >=120 msec.
• Unstable or life threatening cardiac disease: Subjects with any of the following at Screening (Visit 1) would be excluded: Myocardial infarction or unstable angina in the last 6 months; Unstable or life threatening cardiac arrhythmia requiring intervention in the last 3 months; New York Heart Association (NYHA) Class IV Heart failure.
• Antimuscarinic effects: Subjects with a medical condition such as narrow-angle glaucoma, urinary retention, prostatic hypertrophy or bladder neck obstruction should only be included if in the opinion of the Investigator the benefit outweighs the risk and that the condition would not contraindicate study participation.
• Cancer: Subjects with carcinoma that has not been in complete remission for at least 5 years. Subjects who have had carcinoma in situ of the cervix, squamous cell carcinoma and basal cell carcinoma of the skin would not be excluded based on the 5 year waiting period if the subject has been considered cured by treatment.
• Questionable validity of consent: Subjects with a history of psychiatric disease, intellectual deficiency, poor motivation or other conditions that will limit the validity of informed consent to participate in the study.
• Medication prior to spirometry: Subjects who are medically unable to withhold their albuterol/salbutamol for the 6-hour period required prior to spirometry testing at each study visit.
• Tobacco Use: Subjects who are: Current smokers (defined as subjects who have used inhaled tobacco products within the 12 months prior to Visit 1 [i.e., cigarettes, e-cigarettes/vaping, cigars or pipe tobacco]) or former smokers with a smoking history of >=10 pack years (e.g., >=20 cigarettes/day for 10 years).
• Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug abuse within the last 2 years.
• Allergy or Hypersensitivity: A history of allergy or hypersensitivity to any corticosteroid, anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or magnesium stearate.
• Non-compliance: Subjects at risk of non-compliance, or unable to comply with the study procedures. Any infirmity, disability, or geographic location that would limit compliance for scheduled visits.
• Affiliation with Investigator site: Study Investigators, sub-Investigators, study coordinators, employees of a participating Investigator or study site, or immediate family members of the aforementioned that is involved with this study.
• Inability to read: In the opinion of the Investigator, any subject who is unable to read and/or would not be able to complete study related materials. Inclusion Criteria for Enrolment
• Inadequately controlled asthma: Subjects with inadequately controlled asthma (ACQ-6 score >=1.5) at Visit 2.
• Percent-predicted FEV1: A best pre-bronchodilator morning (AM) FEV1 >=30% and <90% of the predicted normal value at Visit 2. Predicted values will be based upon the ERS Global Lung Function Initiative
• Liver function tests at Visit 1: alanine aminotransferase (ALT) <2 x upper limit of normal (ULN); alkaline phosphatase <=1.5xULN; bilirubin <=1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
• Compliance with completion of the Daily eDiary reporting defined as completion of all questions/assessments on >=4 of the last 7 days during the run-in period. Exclusion Criteria for Enrolment
• Respiratory Infection: Occurrence of a culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear during the run-in period that led to a change in asthma management or, in the opinion of the Investigator, is expected to affect the subject's asthma status or the subject's ability to participate in the study.
• Severe asthma exacerbation: Evidence of a severe exacerbation during screening or the run-in period, defined as deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days or an in-patient hospitalization or emergency department visit due to asthma that required systemic corticosteroids.
• Asthma medication: Changes in asthma medication (excluding run-in medication and albuterol/salbutamol inhalation aerosol provided at Visit 1).
• Laboratory test abnormalities: Evidence of clinically significant abnormal laboratory tests during screening or run-in which are still abnormal upon repeat analysis and are not believed to be due to disease(s) present. Each Investigator will use his/her own discretion in determining the clinical significance of the abnormality. Inclusion Criteria for Randomization
• Compliance with completion of the Daily eDiary reporting defined as completion of all questions/assessments on >=4 of the last 7 days during the stabilization period. Exclusion Criteria for Randomization
• Respiratory Infection: Occurrence of a culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear during the stabilization period that led to a change in asthma management or, in the opinion of the Investigator, is expected to affect the subject's asthma status or the subject's ability to participate in the study.
• Severe asthma exacerbation: Evidence of a severe exacerbation during enrolment or the stabilization period, defined as deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days or an inpatient hospitalization or emergency department visit due to asthma that required systemic corticosteroids.
• Asthma medication: Changes in asthma medication (excluding stabilization period medication provided at Visit 2 and albuterol/salbutamol inhalation aerosol provided at Visit 1).

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• FF/UMEC/VI (100/31.25/25) mcg
Dry white powder delivered via the ELLIPTA DPI (one inhalation once-daily [QD] in the morning). The ELLIPTA DPI holds 2 individual blister strips with 30 blisters on each strip: the first strip contains FF 100 mcg in each blister and the second strip contains UMEC 31.25 mcg and VI 25 mcg in each blister.
• FF/UMEC/VI (100/62.5/25) mcg
Dry white powder delivered via the ELLIPTA DPI (one inhalation, QD in the morning). The ELLIPTA DPI holds 2 individual blister strips with 30 blisters on each strip: the first strip contains FF 100 mcg in each blister and the second strip contains UMEC 62.5 mcg and VI 25 mcg in each blister.
• FF/UMEC/VI (200/31.25/25) mcg
Dry white powder delivered via the ELLIPTA DPI (one inhalation, QD in the morning). The ELLIPTA DPI holds 2 individual blister strips with 30 blisters on each strip: the first strip contains FF 200 mcg in each blister and the second strip contains UMEC 31.25 mcg and VI 25 mcg in each blister.
• FF/UMEC/VI (200/62.5/25) mcg
Dry white powder delivered via the ELLIPTA DPI (one inhalation, QD in the morning). The ELLIPTA DPI holds 2 individual blister strips with 30 blisters on each strip: the first strip contains FF 200 mcg in each blister and the second strip contains UMEC 62.5 mcg and VI 25 mcg in each blister.
• FF/VI (100/25) mcg
Dry white powder delivered via the ELLIPTA DPI (one inhalation, QD in the morning). The ELLIPTA DPI holds 2 individual blister strips with 30 blisters on each strip: the first strip contains FF 100 mcg in each blister and the second strip contains VI 25 mcg in each blister.
• FF/VI (200/25) mcg
Dry white powder delivered via the ELLIPTA DPI (one inhalation, QD in the morning). The ELLIPTA DPI holds 2 individual blister strips with 30 blisters on each strip: the first strip contains FF 200 mcg in each blister and the second strip contains VI 25 mcg in each blister.
• Fluticasone/salmeterol (FSC)
Dry white powder delivered via the DISKUS DPI (one inhalation twice daily: one in the morning and one in the evening). The DISKUS DPI holds a strip of 60 blisters; each blister contains FP 250 mcg and 50 mcg of salmeterol.
• Albuterol/salbutamol
This is a rescue medication administered via metered-dose inhaler (MDI) which will be used when needed during the study.

Device:
• ELLIPTA DPI
The ELLIPTA device will be used during the stabilization period and the treatment period. The ELLIPTA DPI is a moulded plastic two-sided device that can hold two individual blister strips which contain powder formulation for oral inhalation.
• DISKUS DPI
The DISKUS device will be used during the run-in period. The DISKUS DPI is a plastic inhalation delivery system containing a single-foil blister strip of a powder formulation of FSC for oral inhalation.
• METERED-DOSE INHALER (MDI)
Albuterol/salbutamol (rescue medication) will be delivered via metered-dose inhaler (MDI) will be used for reversibility testing.

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Berazategui
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Argentina	GSK Investigational Site	Cordoba
Argentina	GSK Investigational Site	Cordoba	Córdova
Argentina	GSK Investigational Site	Florida	Buenos Aires
Argentina	GSK Investigational Site	Mar del Plata	Buenos Aires
Argentina	GSK Investigational Site	Mendoza
Argentina	GSK Investigational Site	Mendoza
Argentina	GSK Investigational Site	Paraná	Buenos Aires
Argentina	GSK Investigational Site	Rosario	Santa Fe
Argentina	GSK Investigational Site	Rosario	Santa Fe
Argentina	GSK Investigational Site	Rosario	Santa Fe
Argentina	GSK Investigational Site	San Rafael	Mendoza
Argentina	GSK Investigational Site	Santa Fe
Argentina	GSK Investigational Site	Tucuman
Australia	GSK Investigational Site	Bedford Park	South Australia
Australia	GSK Investigational Site	Clayton	Victoria
Australia	GSK Investigational Site	Coffs Harbour	New South Wales
Australia	GSK Investigational Site	Golden Beach
Australia	GSK Investigational Site	Melbourne	Victoria
Australia	GSK Investigational Site	Murdoch	Western Australia
Australia	GSK Investigational Site	Randwick	New South Wales
Australia	GSK Investigational Site	Sherwood	Queensland
Australia	GSK Investigational Site	Westmead	New South Wales
Canada	GSK Investigational Site	Ajax	Ontario
Canada	GSK Investigational Site	Brampton	Ontario
Canada	GSK Investigational Site	Burlington	Ontario
Canada	GSK Investigational Site	Hamilton	Ontario
Canada	GSK Investigational Site	London	Ontario
Canada	GSK Investigational Site	Mississauga	Ontario
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Québec
Canada	GSK Investigational Site	Saint John's	Newfoundland and Labrador
Canada	GSK Investigational Site	Sarnia	Ontario
Canada	GSK Investigational Site	St. Charles-Borromee	Quebec
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Trois Rivières	Quebec
Canada	GSK Investigational Site	Victoriaville	Quebec
Canada	GSK Investigational Site	Waterloo	Ontario
Canada	GSK Investigational Site	Windsor	Ontario
Canada	GSK Investigational Site	Windsor	Ontario
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Darmstadt	Hessen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Geesthacht	Schleswig-Holstein
Germany	GSK Investigational Site	Gelsenkirchen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Koblenz	Rheinland-Pfalz
Germany	GSK Investigational Site	Leipzg	Sachsen
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Luebeck	Schleswig-Holstein
Germany	GSK Investigational Site	Neu-Isenburg	Hessen
Germany	GSK Investigational Site	Rheine	Nordrhein-Westfalen
Germany	GSK Investigational Site	Schleswig	Schleswig-Holstein
Italy	GSK Investigational Site	Bari	Puglia
Italy	GSK Investigational Site	Civitanova Marche (MC)	Marche
Italy	GSK Investigational Site	Eboli (SA)	Campania
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Orbassano (TO)	Piemonte
Italy	GSK Investigational Site	Palermo	Sicilia
Italy	GSK Investigational Site	Parma	Emilia-Romagna
Italy	GSK Investigational Site	Pavia	Lombardia
Italy	GSK Investigational Site	Pisa	Toscana
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Tradate (VA)	Lombardia
Japan	GSK Investigational Site	Aichi
Japan	GSK Investigational Site	Aichi
Japan	GSK Investigational Site	Chiba
Japan	GSK Investigational Site	Fukui
Japan	GSK Investigational Site	Fukui
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Gifu
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hyogo
Japan	GSK Investigational Site	Hyogo
Japan	GSK Investigational Site	Hyogo
Japan	GSK Investigational Site	Hyogo
Japan	GSK Investigational Site	Ibaraki
Japan	GSK Investigational Site	Ibaraki
Japan	GSK Investigational Site	Ibaraki
Japan	GSK Investigational Site	Ibaraki
Japan	GSK Investigational Site	Ibaraki
Japan	GSK Investigational Site	Kagawa
Japan	GSK Investigational Site	Kagawa
Japan	GSK Investigational Site	Kagawa
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Kyoto
Japan	GSK Investigational Site	Kyoto
Japan	GSK Investigational Site	Kyoto
Japan	GSK Investigational Site	Kyoto
Japan	GSK Investigational Site	Mie
Japan	GSK Investigational Site	Miyagi
Japan	GSK Investigational Site	Miyagi
Japan	GSK Investigational Site	Miyagi
Japan	GSK Investigational Site	Miyagi
Japan	GSK Investigational Site	Miyagi
Japan	GSK Investigational Site	Nagano
Japan	GSK Investigational Site	Nagasaki
Japan	GSK Investigational Site	Nara
Japan	GSK Investigational Site	Oita
Japan	GSK Investigational Site	Okayama
Japan	GSK Investigational Site	Okinawa
Japan	GSK Investigational Site	Okinawa
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Saga
Japan	GSK Investigational Site	Saitama
Japan	GSK Investigational Site	Saitama
Japan	GSK Investigational Site	Shimane
Japan	GSK Investigational Site	Shizuoka
Japan	GSK Investigational Site	Shizuoka
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Toyama
Japan	GSK Investigational Site	Yamagata
Japan	GSK Investigational Site	Yamagata
Japan	GSK Investigational Site	Yamaguchi
Japan	GSK Investigational Site	Yamanashi
Korea, Republic of	GSK Investigational Site	Busan
Korea, Republic of	GSK Investigational Site	Cheongju-si, Chungcheongbuk-do
Korea, Republic of	GSK Investigational Site	Daegu
Korea, Republic of	GSK Investigational Site	Daegu
Korea, Republic of	GSK Investigational Site	Daejon
Korea, Republic of	GSK Investigational Site	Gwangju
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Suwon-si, Gyeonggi-do
Korea, Republic of	GSK Investigational Site	Wonju-si, Kanwon-do
Netherlands	GSK Investigational Site	Alkmaar
Netherlands	GSK Investigational Site	Almere
Netherlands	GSK Investigational Site	Beek
Netherlands	GSK Investigational Site	Breda
Netherlands	GSK Investigational Site	Eindhoven
Netherlands	GSK Investigational Site	Hengelo
Netherlands	GSK Investigational Site	Leiden
Netherlands	GSK Investigational Site	Rotterdam
Netherlands	GSK Investigational Site	Rotterdam
Netherlands	GSK Investigational Site	Rotterdam
Netherlands	GSK Investigational Site	Utrecht
Poland	GSK Investigational Site	Bialystok
Poland	GSK Investigational Site	Bydgoszcz
Poland	GSK Investigational Site	Grudziadz
Poland	GSK Investigational Site	Koscian
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Lublin
Poland	GSK Investigational Site	Ostrowiec Swietokrzyski
Poland	GSK Investigational Site	Poznan
Poland	GSK Investigational Site	Rzeszow
Poland	GSK Investigational Site	Slupsk
Poland	GSK Investigational Site	Sopot
Poland	GSK Investigational Site	Szczecin
Poland	GSK Investigational Site	Tarnow
Poland	GSK Investigational Site	Zgierz
Romania	GSK Investigational Site	Bacau
Romania	GSK Investigational Site	Brasov
Romania	GSK Investigational Site	Brasov
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Cluj Napoca
Romania	GSK Investigational Site	Cluj Napoca
Romania	GSK Investigational Site	Cluj Napoca
Romania	GSK Investigational Site	Craiova
Romania	GSK Investigational Site	Deva
Romania	GSK Investigational Site	Galati
Romania	GSK Investigational Site	Iasi
Romania	GSK Investigational Site	Oradea
Romania	GSK Investigational Site	Pitesti
Romania	GSK Investigational Site	Slobozia
Romania	GSK Investigational Site	Suceava
Romania	GSK Investigational Site	Targu Mures
Romania	GSK Investigational Site	Timisoara
Romania	GSK Investigational Site	Timisoara
Russian Federation	GSK Investigational Site	Arkhangelsk
Russian Federation	GSK Investigational Site	Belgorod
Russian Federation	GSK Investigational Site	Blagoveshchensk
Russian Federation	GSK Investigational Site	Chelyabinsk
Russian Federation	GSK Investigational Site	Chita
Russian Federation	GSK Investigational Site	Ekaterinburg
Russian Federation	GSK Investigational Site	Irkutsk
Russian Federation	GSK Investigational Site	Ivanovo
Russian Federation	GSK Investigational Site	Izhevsk
Russian Federation	GSK Investigational Site	Kazan
Russian Federation	GSK Investigational Site	Kemerovo
Russian Federation	GSK Investigational Site	Kemerovo
Russian Federation	GSK Investigational Site	Khantymansiysk
Russian Federation	GSK Investigational Site	Krasnodar
Russian Federation	GSK Investigational Site	Krasnoyarsk
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Orenburg
Russian Federation	GSK Investigational Site	Perm
Russian Federation	GSK Investigational Site	Petrozavodsk
Russian Federation	GSK Investigational Site	Saint Petersburg
Russian Federation	GSK Investigational Site	Saint-Petersburg
Russian Federation	GSK Investigational Site	Saint-Petersburg
Russian Federation	GSK Investigational Site	Saint-Petersburg
Russian Federation	GSK Investigational Site	Saint-Petersburg
Russian Federation	GSK Investigational Site	Samara
Russian Federation	GSK Investigational Site	Saratov
Russian Federation	GSK Investigational Site	Saratov
Russian Federation	GSK Investigational Site	St Petersburg
Russian Federation	GSK Investigational Site	Tomsk
Russian Federation	GSK Investigational Site	Tomsk
Russian Federation	GSK Investigational Site	Tver
Russian Federation	GSK Investigational Site	Ufa
Russian Federation	GSK Investigational Site	Ulan-Ude
Russian Federation	GSK Investigational Site	Ulyanovsk
Russian Federation	GSK Investigational Site	Yaroslavl
Russian Federation	GSK Investigational Site	Yaroslavl
South Africa	GSK Investigational Site	Bellville
South Africa	GSK Investigational Site	Bloemfontein
South Africa	GSK Investigational Site	Cape Town
South Africa	GSK Investigational Site	Durban
South Africa	GSK Investigational Site	Middelburg	Mpumalanga
South Africa	GSK Investigational Site	Mowbray
South Africa	GSK Investigational Site	Panorama
South Africa	GSK Investigational Site	Pretoria West
South Africa	GSK Investigational Site	Reiger Park
South Africa	GSK Investigational Site	Somerset West
South Africa	GSK Investigational Site	Tygerberg
Spain	GSK Investigational Site	Alcobendas	Madrid
Spain	GSK Investigational Site	Badalona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Burgos
Spain	GSK Investigational Site	Centelles
Spain	GSK Investigational Site	Gerona
Spain	GSK Investigational Site	Hospitalet de Llobregat
Spain	GSK Investigational Site	Las Palmas
Spain	GSK Investigational Site	Loja/ Granada
Spain	GSK Investigational Site	Pozuelo De Alarcón/Madrid
Spain	GSK Investigational Site	Salamanca
Spain	GSK Investigational Site	Santander
Spain	GSK Investigational Site	Santiago de Compostela
Spain	GSK Investigational Site	Valladolid
Spain	GSK Investigational Site	Zaragoza
United Kingdom	GSK Investigational Site	Aberdeen	Aberdeenshire
United Kingdom	GSK Investigational Site	Bexhill	Sussex East
United Kingdom	GSK Investigational Site	Blackpool	Lancashire
United Kingdom	GSK Investigational Site	Bradford
United Kingdom	GSK Investigational Site	Corby	Northamptonshire
United Kingdom	GSK Investigational Site	Edgbaston
United Kingdom	GSK Investigational Site	Liverpool.
United Kingdom	GSK Investigational Site	Northwood	Middlesex
United Kingdom	GSK Investigational Site	Romford	Essex
United Kingdom	GSK Investigational Site	Sidcup, Kent
United Kingdom	GSK Investigational Site	Trowbridge
United Kingdom	GSK Investigational Site	Wishaw	Lanarkshire
United States	GSK Investigational Site	Abingdon	Virginia
United States	GSK Investigational Site	Adairsville	Georgia
United States	GSK Investigational Site	Anderson	South Carolina
United States	GSK Investigational Site	Asheville	North Carolina
United States	GSK Investigational Site	Aurora	Colorado
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Aventura	Florida
United States	GSK Investigational Site	Baltimore	Maryland
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Brandon	Florida
United States	GSK Investigational Site	Buffalo	New York
United States	GSK Investigational Site	Canton	California
United States	GSK Investigational Site	Charleston	South Carolina
United States	GSK Investigational Site	Charlotte	North Carolina
United States	GSK Investigational Site	Chevy Chase	Maryland
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Colorado Springs	Colorado
United States	GSK Investigational Site	Columbia	Maryland
United States	GSK Investigational Site	Columbus	Georgia
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Dayton	Ohio
United States	GSK Investigational Site	Denver	Colorado
United States	GSK Investigational Site	Dublin	Ohio
United States	GSK Investigational Site	El Paso	Texas
United States	GSK Investigational Site	Encinitas	California
United States	GSK Investigational Site	Escondico	California
United States	GSK Investigational Site	Gastonia	North Carolina
United States	GSK Investigational Site	Gilbert	Arizona
United States	GSK Investigational Site	Greenville	South Carolina
United States	GSK Investigational Site	Hendersonville	Tennessee
United States	GSK Investigational Site	High Point	North Carolina
United States	GSK Investigational Site	Hollywood	Florida
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Huntersville	North Carolina
United States	GSK Investigational Site	Huntington Beach	California
United States	GSK Investigational Site	Huntington Beach	California
United States	GSK Investigational Site	Jefferson Hills	Pennsylvania
United States	GSK Investigational Site	Jupiter	Florida
United States	GSK Investigational Site	Killeen	Texas
United States	GSK Investigational Site	La Jolla	California
United States	GSK Investigational Site	Lafayette	Colorado
United States	GSK Investigational Site	Lampasas	Texas
United States	GSK Investigational Site	Lincoln	Nebraska
United States	GSK Investigational Site	Little Rock	Arkansas
United States	GSK Investigational Site	Live Oak	Texas
United States	GSK Investigational Site	Long Beach	California
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Louisville	Kentucky
United States	GSK Investigational Site	McKinney	Texas
United States	GSK Investigational Site	Medford	Oregon
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Michigan City	Indiana
United States	GSK Investigational Site	Minneapolis	Minnesota
United States	GSK Investigational Site	Missouri City	Texas
United States	GSK Investigational Site	Mobile	Alabama
United States	GSK Investigational Site	Montgomery	Alabama
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Normal	Illinois
United States	GSK Investigational Site	Ocean City	New Jersey
United States	GSK Investigational Site	Ocoee	Florida
United States	GSK Investigational Site	Oklahoma City	Oklahoma
United States	GSK Investigational Site	Orangeburg	South Carolina
United States	GSK Investigational Site	Owensboro	Kentucky
United States	GSK Investigational Site	Oxnard	California
United States	GSK Investigational Site	Pharr	Texas
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	Plano	Texas
United States	GSK Investigational Site	Portland	Oregon
United States	GSK Investigational Site	Portland	Oregon
United States	GSK Investigational Site	Raleigh	North Carolina
United States	GSK Investigational Site	Richmond	Virginia
United States	GSK Investigational Site	River Forest	Illinois
United States	GSK Investigational Site	Rochester	Michigan
United States	GSK Investigational Site	Rolling Hills Estates	California
United States	GSK Investigational Site	Roseville	California
United States	GSK Investigational Site	Saint Charles	Missouri
United States	GSK Investigational Site	Saint Petersburg	Florida
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	San Jose	California
United States	GSK Investigational Site	Scottsdale	Arizona
United States	GSK Investigational Site	Seattle	Washington
United States	GSK Investigational Site	Shelby	North Carolina
United States	GSK Investigational Site	South Bend	Indiana
United States	GSK Investigational Site	Spartanburg	South Carolina
United States	GSK Investigational Site	Spartanburg	South Carolina
United States	GSK Investigational Site	Sunset	Louisiana
United States	GSK Investigational Site	Tallahassee	Florida
United States	GSK Investigational Site	Topeka	Kansas
United States	GSK Investigational Site	Tucson	Arizona
United States	GSK Investigational Site	Waco	Texas
United States	GSK Investigational Site	Warwick	Rhode Island
United States	GSK Investigational Site	Williamsburg	Virginia
United States	GSK Investigational Site	Wilmington	North Carolina
United States	GSK Investigational Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  Germany,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Romania,  Russian Federation,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 24	FEV1 is a measure of lung function and is defined as the maximal volume of air that can be forcefully exhaled in one second. Trough FEV1 on treatment is defined as the highest FEV1 value obtained prior to the morning dose of investigational product. Baseline value is the last acceptable/borderline acceptable pre-dose FEV1 prior to randomized treatment start date (pre-dose at Day 1). Change from Baseline value is the value at Week 24 minus the Baseline value. Intent-to-Treat (ITT) Population comprised of all randomized participants, excluding those who were randomized in error, who did not receive the study drug. Treatment policy estimand was assessed, including all on- and post-treatment data. Different participants may have been analyzed at different time points; thus, overall number of participants analyzed reflects everyone in ITT Population without missing covariate information, with Baseline and at least one post-baseline measurement. Mixed Model Repeated Measures(MMRM) was used.	Baseline (pre-dose at Day 1) and Week 24
Secondary	Annualized Rate of Moderate and Severe Asthma Exacerbations	A moderate asthma exacerbation is considered to be a deterioration in asthma symptoms or in lung function, or increased rescue bronchodilator use lasting for at least 2 days or more, but not be severe enough to warrant systemic corticosteroid use (or a doubling or more of the maintenance systemic corticosteroid dose, if applicable) for 3 days or more and/or hospitalization. It is an event that, when recognized, should result in a temporary change in treatment, to prevent it from becoming severe. A severe asthma exacerbation is defined as the deterioration of asthma requiring the use of systemic corticosteroids (tablets,suspension or injection), or an increase from a stable maintenance dose (For participants receiving maintenance systemic corticosteroids, at least double the maintenance systemic corticosteroid dose for at least 3 days is required), for at least 3 days or an inpatient hospitalization or emergency department visit because of asthma, requiring systemic corticosteroids.	Up to Week 52
Secondary	Mean Change From Baseline in Clinic FEV1 at 3 Hours Post Study Treatment at Week 24	FEV1 is a measure of lung function and is defined as the maximal volume of air that can be forcefully exhaled in one second. Baseline value is the last acceptable/borderline acceptable pre-dose FEV1 prior to randomized treatment start date (pre-dose at Day 1). Change from Baseline value is the value at Week 24 (recorded at 3 hours post dose) minus the Baseline value.	Baseline (pre-dose at Day 1) and 3 hours post dose at Week 24
Secondary	Mean Change From Baseline in Asthma Control Questionnaire-7 (ACQ-7) Total Score at Week 24	The ACQ-7 consists of 7 attributes of asthma control, of which 6 to be self-completed by participant in a 6-item questionnaire, enquire about frequency and/or severity of symptoms over the previous week on: nocturnal awakening, symptoms on waking in the morning, activity limitation, shortness of breath, wheeze, and rescue medication use. The seventh attribute measures the lung function, which was included via pre-bronchodilator FEV1 % predicted value. All 7 items of ACQ have response on 0-6 ordinal scale (0=no impairment/limitation, 6=total impairment/limitation). The total score is calculated as the average of all non-missing item responses, ranges from 0 to 6. Higher score indicates worst symptoms. Treatment policy estimand was assessed, including all on- and post-treatment data. Baseline value was at randomization visit (pre-dose,Day 1). Change from Baseline was defined as value at Week 24 minus Baseline value.	Baseline (pre-dose at Day 1) and Week 24
Secondary	Mean Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score at Week 24	The SGRQ had 50 questions (scored from 0 to 100 where 0 indicates best and 100 indicates worst health) designed to measure quality of life (QoL) of participants with airway obstruction, measuring symptoms, impact, and activity. The questions are designed to be self-completed by the participant with a recall over the past 3 months. SGRQ total score was calculated by summing the pre-assigned weights of answers, dividing by the sum of the maximum weights for items in SGRQ and multiplying by 100. SGRQ total score ranges from 0 to 100 where 0 indicates best and 100 indicates worst health. A change of 4 points is considered a clinically relevant change. Treatment policy estimand was assessed, including all on- and post-treatment data. Baseline value was at randomization visit (pre-dose at Day 1). Change from Baseline value is the value at Week 24 minus the Baseline value.	Baseline (pre-dose at Day 1) and Week 24
Secondary	Mean Change From Baseline in Evaluating Respiratory Symptoms (E-RS) Total Score Over Weeks 21 to 24 (Inclusive) of the Treatment Period	The E-RS in Chronic Obstructive Pulmonary Disease (COPD) consists of 11 items. E-RS captures information related to respiratory symptoms, i.e. breathlessness, cough, sputum production, chest congestion and chest tightness. The E-RS was completed daily and data was derived by 4-weekly intervals, requiring at least 50% of data to be present during a period. 7 items are scored from 0 (not at all) to 4 (extreme) and 4 items are scored from 0 (not at all) to 3 (extreme). The E-RS total score was calculated by taking sum of all the items. The E-RS total score has a scoring range of 0 to 40, with higher scores indicating more severe respiratory symptoms. Treatment policy estimand was assessed, including all on- and post-treatment data. Baseline value was the mean value of 14 days prior to randomization. Change from Baseline was calculated as post-baseline value (mean of daily E-RS total scores during Week 21 to 24 ) minus Baseline value.	Baseline (14 days prior to randomization) and Weeks 21 to 24
Secondary	Number of Participants With Any Serious Adverse Event (SAE) and Common (>=3%) Non-SAE	Adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, events associated with liver injury and impaired liver function, or any other situation according to medical or scientific judgment were categorized as SAE. Number of participants with any SAE and common (>=3%) non-SAEs are presented.	Up to Week 52
Secondary	Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Twelve-lead ECGs were performed during the study using an automated ECG machine. All ECG measurements were made with the participant in a supine position having rested in this position for approximately 5 minutes before each reading. The number of participants with worst case post-Baseline abnormal ECG findings were reported.	Up to Week 52
Secondary	Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 24	Blood pressure (systolic and diastolic) was measured in the sitting position after approximately 5 minutes rest. Baseline value is the last acceptable/borderline acceptable value prior to randomized treatment start date (pre-dose at Day 1). Change from Baseline value is the value at the clinic visit minus the Baseline value. Different participants may have been analyzed at different time points; thus, overall number of participants analyzed reflects everyone in ITT Population without missing covariate information, with Baseline and at least one post-baseline measurement.	Baseline (pre-dose at Day 1) and Week 24
Secondary	Mean Change From Baseline in Pulse Rate at Week 24	Pulse Rate was measured in the sitting position after approximately 5 minutes rest. Baseline value is the last acceptable/borderline acceptable value prior to randomized treatment start date (pre-dose at Day 1). Change from Baseline value is the value at the clinic visit minus the Baseline value. Different participants may have been analyzed at different time points; thus, overall number of participants analyzed reflects everyone in ITT Population without missing covariate information, with Baseline and at least one post-baseline measurement.	Baseline (pre-dose at Day 1) and Week 24
Secondary	Number of Participants With Abnormal Clinical Chemistry Values	Blood samples were collected for assessment of clinical chemistry parameters, which included albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), direct bilirubin, total bilirubin, calcium, creatinine, glucose, potassium, protein, sodium and urea. Abnormal laboratory results are categorized as high or low with respect to their normal ranges. Participants having High and Low values from normal ranges for any parameter at any time post-baseline visits are presented.	Up to Week 52
Secondary	Number of Participants With Abnormal Hematology Values	Blood samples were collected for assessment of hematology parameters, which included Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Platelets, Mean Corpuscular Hemoglobin (MCH) and Mean Corpuscular Volume (MCV). Abnormal laboratory results are categorized as high or low with respect to their normal ranges. Participants having High and Low values from normal ranges for any parameter at any time post-baseline visits are presented.	Up to Week 52